Process of alkylating pyridines



. 2,786,846 PROCESS OF ALKYL'ATING PYRIDINES No Drawing. Application June 1, 1953, Serial No. 358,953

4 Claims. (01.260-290 Our present invention relates to a process of alkylating United S t,- ates Pateii't O The Chiehibabin meth a methyl group attached at the 2-position, the 4-position,

or the 6-position of a pyridine nucleus. More specifically, our invention relates to the alkylation of a methyl group of 2-picoline, 4-picoline, 2,4-lutidine, 2,5-lutidine, 2,6- lutidine, 2-methyl-S-ethylpyridine, 2-methyl-3-ethylpyridine, 2-methyl-5,6-benzopyridine, and 4-methyl-5,6 -benz'o pyridine.

This application is a continuation-in-part of our co pending application Serial Number 161,736, filed May 12, 1950, and now abandoned.

By alkylating a methyl group we mean converting the methyl group into an alkyl or alkenyl group having two or more carbon atoms.

The alkylation of pyridines has been investigatedby many researchers. In 1942 Arens and Wibaut disclosed (Rec. trav. chim. pyridine. They found that alkyl groups may be introduced into the 4-position of pyridine by the action of zinc dust on a mixture of pyridine, organic acid anhydride, and the corresponding organic acid. Thus, they prepared 4-ethylpyridine from pyridine acetic anhydride, andacetic acid; 4-propylpyridine was prepared by using zinc 'dust, propi onic acid, and propionic anhydride. This reaction of Arens wibaut is of limited application. It can be'used for the introduction of. an I 61, 59-68) a process of alkylating J- by the action of zinc dust',

alkyl group into the 4-position only. FurthermOre QQ-it an alkyl group into the Z-arninopyridine, picolinic cannot be used to introduce 4-position of Z-methylpyridine, acid, nor of'2-chloropyridine. H l In 1950, Rieger (U. S. Pat. 2,502,174) described a process of alkylating pyridine by the use of organic salts of tetravalent lead. By this process alkyl groups containing one less carbon atom than the acid radical of the lead salt are attached to the pyridine nucleus; the alkyl group enters both the 2- and the 4-positions if those are open. Thus, treatment of pyridine with lead tetra-acetate gives a mixture of 2-picoline and 4-picoline. If the 2-positions are blocked, the entering alkyl group occupies the 4-position, thus 2,6-lutidine and lead tetra-acetate gives 2,4,6-collidine. If the 4-position is blocked, the entering alkyl group takes the 2-position; 4-picoline with lead tetra-acetate gives 2,4-lutidine. While the Rieger method is useful for the preparation of some alkylpyridines, such as 2,4-lutidine from 4-picoline, it is not a practical method for the commercial production of such alkylpyridines as Z-propylpyridine or 4-ethylpyridine.

The Russian chemist Chichibabiu had developed a useful method for preparing 2- and 4-alkylpyridines from 2-picoline and 4-picoline. This method, which was published in 1936 (Bull. soc. chirn. France 3, 1607-32) involves reacting a 2-picoline or a 4-picoline with sodamide and then with an alkyl halide. The method has been applied to the preparation of 2'ethylpyridine from Z-picoline and methyl chloride as well as to the preparation of long-chain alkylpyridines, such as Z-n-tridecylpyridine, from Z-picoline and n-dodecylchloride (Knight and "2,786,846 Baitented Mar. 26, 1957 ICC : ticularly adaptable for commercial processes. The yields are not too satisfactory, and the reagents are expensive.

Since various pyridines having a methyl group in the Z-pbsitibn or the 4-position are commercially available, we undertookto develop a simple, commercially practical, method of producing alkylpyridines. from the readily available 2picolines and 4-picolines.. That we were successful is clearly evident from the description ofour invention given below.

We have found attached to the pyridine ring at the. 2-position, or at the 4-position, or at the 6-position by mixing the methylpyridinewith an aliphatic aldehyde, vaporizing the, resultant mixture and passing the vapors through a suitable reactor containing a catalyst, maintained at a reacting temperature preferably between 200 C. and 550 C., and more desirably between 250 C. and500 C. We prefer to carry out our process in a continuous manner although that is-not necessary.

In accordance with our process, the alkylation of Z-methylpyridine with formaldehyde results in the formation of 2-ethylpyridine and Z-ethenylpyridine (commonly known as 2-vinylpyridine). Alkylation with acetaldehyde yields 2-propylpyridine .tand; -2+propenylpyridine. Pro: pionaldehyde gives 2-butylpyridine and Z-butenylpyridine in relatively poorer yields.

Since the methyl groups of 2,6-lutidine are' identical, one might anticipate that each of them would react in the manner of the methyl group of 2-methylpyridine. In accordance with our process, the alkylation of 2,6- lutidine with formaldehyde 'results mainly in the alkylation. or only onej'jof the methyl" groups. We rave not isolated any 'dialkylat ion product, but it is entirely possible thata srnall amount was formed.

4-methylpyridine is alkylated in accordance with our process to'g ive 4-alkylpyridines and 4-alkenylpyridinesl In the case of 2,4,6-trimethylpyridine we are presented with three methyl groups which are potentially capable of alkylation by our process. W e find, however,,that-2,4; 6'- trimethylpyridine is alkylated by formaldehyde almost exclusively in the 2-position. This is in contrast to the Chichibabin process; reacting 2,4,6-trimethylpyridine with sodamide and then with an alkyl halide results in the alkylation of the methyl group in the 4-position. Neither the Arens-Wibaut method of alkylation, nor the Rieger process will alkylate 2,4,6-trimethylpyridine.

The methyl group of Z-methyl-S-ethylpyridine may be alkylated in accordance with our process to give 2-alkyl- S-ethylpyridines and 2-alkenyl-S-ethylpyridines. We have observed no alkylation of the ethyl group in the 5-position.

In carrying out our invention, we may use various types of reactors. We prefer the fluid catalyst type, such as is normally used in carrying out cracking operations in the petroleum industry. Such reactors are of tubular form with suitable connections at entrance and exit. They are provided with means for supporting the fluid bed of catalyst and are provided with any convenient means for heating them.

We may use any of a large number of catalysts in carrying out our process, for example, we can use alumina as a catalyst; or we can use the alumina mixed with zinc fluoride.

A highly satisfactory way of carrying out our invention is described more fully by means of the following specific examples. These examples are only for purposes of illustration.

that we can alkylate a methyl group Example 1 We vaporize a mixture composedof one mole of 2- picolinc and one mole of fprrnaldehyde (the formaldehitdeused isa 37% aquedufssolution) an pass the vapor through a suitable reactcrcofitaining a fluidized catalytic e of alu in HA1) which had been imp gna d. with 10% zinc fl oride; the ata ys is finely ivided and all at i passes through 10.0 mesh- ..The rea or is m n ined at a emp rature er abou 275 C. The superficial velocity at which the vapors are passed through the ca alys is about 0. fo t per s cond. As h mix r f 2- picoline and formaldehyde passes through the reactor, a reaction .occurs whereby 2-vinylpyridine and a small amountof Z-ethylpyr'idine. are produced. The vapors of the unchanged reactants and the reaction products are promptly taken. out of the reactor and are promptly condensed, cooled, and collected in a suitable receiver.

The Z-VinyIpyridine .is separated from the 2-ethylpyridine and unreacted Z-picoline and formaldehyde and from the other reaction products in any suitable manner, as, for example, by fractional distillation under vacuum.

The yield .of 2-yjnylpyridine and its purity is high.

Example 2 Example 3 The pr cess of Examp .1 is repe ted with the tion tha the piccline used. Angelin vinylpyridine is produced.

Example 4 The process at Eaample. 1 is repeated with the .ex eption that the temp .418 of the reactor is 4.0.0 instead of the 275 C. used in Example 1. By carrying out the. process in. this manner. there results .a mixture of z ethy nyridine and l-vinylpyridine, wi h h Z-cthylpyridine. 'rcdoclin ins. .hylpyridine and the 2- i 1n the reaction mixture inyl yndlnema .s .f crn each other in any suitable manner as y fra iQn under vacuum excep- By this process and tional di.

resultant ethylpyridine.

Example 5 The process of Example 2 is repeated with the d'iflference that the reactor temperature is 275 C. instead of the 400 C. used in Example 2. This process yields a mixture of 2-ethylpyridine and 2vinylpyridine, with the 2-vinylpyridine predominating. The Z-ethylpyridine and the 2-vinylpyridine can be separated from the reaction mixture and from each other by fractional distillation under vacuum.

Example .6

The process of Example 2 is repeated with the exception that the picoline used. is 4-pico1ine. By this process 4-ethylpyridine is produced.

We have found that higher yields of alkenylpyridine as ccmpared to alkylpyridine, are produced if the term perature of the reactor is maintained at about 250 C.

to 300 C. We have also found that the ratio of alkyl pyridine to alkenylpyridine is increased if the reactor temperature is maintained at about 400 C. to 550 C.

- We claim asour invention:

1.. The process of producing a compound of the class consisting of a 'Z-ethylpyridine and a 4-ethylpyridine 1'. hi h gomprises the vapor phase reaction of a compound oiihe class consisting otgpicoline, 4-picoline, alkyl-Z- picoline, and alkyl-4-picoline with formaldehyde at a temperaturebetween about 400- C. to about 550 C. in the presence of alumina 2.. The process of claim 1 in which the picoline is 2- picoiine 3. The process of claim 1 in which the picoline is 4- Dico'lirieprocess of alkylating a methyl group of abomcat-alyst and recovering the 5 pound of the class consisting of Lpicoline, 4-picoline, j alkyl 2 picoline, and alkyl-4-picoline which comprises the vapor phase reaction of the picoline with a lower aliphatic aldehyde at a temperature between about 400 C.

to about 550 in the presence of an alumina catalyst and recovering the resultant. alkylpicoline.

Retereuces Cited in the. file of this patent UNITED STATES PATENTS 2,512,660 Mahan June 27, 1950 2,534,285 Mahan Dec. 19, 1950 2,556,845 Kauffman June 12, 1951 2,611,769 Hays Sept. 23, 1952 2,698,848 Mahan Jan. 4, 1955 

4. THE PROCESS OF ALKYLATING A METHYL GROUP OF A COMPOUND OF THE CLASS CONSISTING OF 2-PICOLINE, 4-PICOLINE, ALKYL-2-PICOLINE, AND ALKYL-4-PUCOLINE WHICH COMPRISES THE VAPOR PHASE REACTION OF THE PICOLINE WITH A LOWER ALIPHATIC ALDEHYDE AT A TEMPERATURE BETWEEN ABOUT 400*C. TO ABOUT 550*C. IN THE PRESENCE OF AN ALUMINA CATALYST AND RECOVERING THE RESULTANT ALKYLPICOLINE. 